CIP COMPREHENSIVE QUESTIONS AND ANSWERS
SET A+
✔✔Guardian - ✔✔An individual who is authorized under applicable state or local law to
consent on behalf of a child to general medical care.
✔✔Assent - ✔✔A child's affirmative agreement to participate in research. The
regulations do not indicate an age at which this ought to be possible.
✔✔Prisoner - ✔✔Any individual involuntarily confined or detained in a penal institution,
including situations where a human subject becomes one after the research has
commenced.
✔✔Minimal Risk as Defined in Subpart C - ✔✔The probability and magnitude of
physical or psychological harm that is normally encountered in the daily lives, or in the
routine medical, dental, or psychological examination of healthy persons. In non-
prisoner research, IRBs consider a wide range of risks, representing the possibility of
physical, psychological, social, economic, or legal harms. In Subpart C, however, only
physical or psychological harm is mentioned.
✔✔Component Analysis - ✔✔An ethical analysis of risks and benefits built on the
recognition that clinical research often contains a mixture of therapeutic and non-
therapeutic procedures and that separate moral standards are required for each.
✔✔Treatment IND - ✔✔Investigational drugs are allowed to be used for treatment of a
single patient while Phase II/III studies are still underway only when the manufacturer
agrees to provide the drug and the FDA issues this patient-specific IND.
✔✔Emergency Use IND - ✔✔A special category of drugs for studies invoking the
special waiver of consent for treatment studies in an emergency setting. A set of rules
under which therapeutic trials in an emergency setting can be done. These rules
provide for a community consultation in lieu of individualized consent and restrict the
research to a very serious condition under circumstances that preclude getting
surrogate consent in a timely manner.
,✔✔Anonymous Samples - ✔✔Samples collected without direct identifiers and involve
the lowest level of risk.
✔✔Anonymized Samples - ✔✔Samples that were originally collected with direct
identifiers and from which the identifiers have been irretrievably stripped from the
sample and replaced with a random code.
✔✔Identified Samples - ✔✔Samples in which the identity of the donors can be readily
ascertained.
✔✔Coded or Linked Samples - ✔✔Samples where the direct identifier is replaced with a
code and a key to the code exists. These samples are the most used in research.
✔✔Placebo - ✔✔Any medical treatment that is inactive for the condition being
evaluated other than the effect which may result from a person's thinking that he or she
may be receiving an active treatment.
✔✔Historical Control Group - ✔✔A control group that is chosen from studies that were
completed in the past.
✔✔Noninferiority Trial - ✔✔A trial that uses active treatment control where the goal is to
show that the study drug is not less effective than the control by more than a defined
amount.
✔✔Intrapatient Dose Escalation - ✔✔A dosing scheme that allows patients to be given
successively higher doses of an experimental drug if the initial dose administered
proves to be well tolerated but unable to achieve the efficacy target.
✔✔Benefit - ✔✔The positive value or advantage of being part of the research study.
✔✔Nuremberg Code - ✔✔Ten points (not law) determined to be essential for
conducting research with humans. Summarized, they include:
*Informed consent
*Research should be based on prior animal work
*Risks should be justified by anticipated benefits
*Only qualified scientists may conduct research
*Physical/mental suffering must be avoided
*Research in which death or disabling injury is expected should not be conducted
✔✔Declaration of Helsinki - ✔✔1964 World Medical Association code of research ethics
that reinterpreted Nuremberg Code, specifically with regard to clinical trials with
therapeutic intent. Subsequently, journal editors required research be conducted in
accordance with the declaration.
, ✔✔Beecher Article - ✔✔1966 Dr. Henry K Beecher (anesthesiologist) wrote an article in
NEJM describing 22 studies with controversial ethics that had been conducted by
reputable researchers and published in major journals.
✔✔Willowbrook Hepatitis Study - ✔✔1956 Willowbrook - an institution for mentally
retarded children - initiated a study to determine the natural history of viral hepatitis, and
to test the effectiveness of gamma globulin as an agent for innoculating against
hepatitis. Children were deliberately infected with a mild form of hepatitis. Ethical
problems: exploitation of vulnerable population, withholding risk information, coercion.
✔✔Jewish Chronic Disease Study - ✔✔1963 liver cancer cells were injected into senile
patients without their knowledge as part of a study of immunity to cancer. Researchers
believed cells would be rejected, so did not think it was necessary to frighten the
patients by telling them. Ethical problems: lack of informed consent, vulnerable
population.
✔✔San Antonio Contraception Study - ✔✔1971 Mexican-American women seeking
contraceptives from a clinic participated in a study that involved taking oral birth control
then crossover to placebo. Subjects were not informed of the crossover. Ten of 76
participants became pregnant. Ethical problems: lack of informed consent, vulnerable
population, risks outweighed benefits.
✔✔Milgram Study - ✔✔1963 a series of social psychology experiments conducted by
Yale University psychologist Stanley Milgram. They measured the willingness of study
participants, men from a diverse range of occupations with varying levels of education,
to obey an authority figure who instructed them to perform acts conflicting with their
personal conscience (administering electric shocks to a subject who was allied with the
research and who pretended to feel pain) ; the experiment found, unexpectedly, that a
very high proportion of people were prepared to obey, albeit unwillingly, even if
apparently causing serious injury and distress. Ethical problems: deception,
unanticipated psychological harms
✔✔Public Health System Syphilis Study - ✔✔1932-1971 PHS study designed to
document the natural history of syphilis in African-American men. At the time the study
was initiated, there was no known treatment for syphilis. Men were recruited without
truly informed consent, and received "treatments" such as spinal taps that had no real
curative intent. After penicillin was found to be safe and effective treatment for syphilis
in the 1940s, the men in the study were denied antibiotics. The study resulted in 28
deaths, 100 cases of disability and 19 cases of congenital syphilis. Ethical problems:
lack of informed consent, deception, withholding information, withholding treatment,
putting men and their families at risk, exploitation of a vulnerable population who would
not benefit from participation.
✔✔The National Commission/The National Research Act - ✔✔1974 Congress
authorized the formation of the National Commission for the Protection of Human
SET A+
✔✔Guardian - ✔✔An individual who is authorized under applicable state or local law to
consent on behalf of a child to general medical care.
✔✔Assent - ✔✔A child's affirmative agreement to participate in research. The
regulations do not indicate an age at which this ought to be possible.
✔✔Prisoner - ✔✔Any individual involuntarily confined or detained in a penal institution,
including situations where a human subject becomes one after the research has
commenced.
✔✔Minimal Risk as Defined in Subpart C - ✔✔The probability and magnitude of
physical or psychological harm that is normally encountered in the daily lives, or in the
routine medical, dental, or psychological examination of healthy persons. In non-
prisoner research, IRBs consider a wide range of risks, representing the possibility of
physical, psychological, social, economic, or legal harms. In Subpart C, however, only
physical or psychological harm is mentioned.
✔✔Component Analysis - ✔✔An ethical analysis of risks and benefits built on the
recognition that clinical research often contains a mixture of therapeutic and non-
therapeutic procedures and that separate moral standards are required for each.
✔✔Treatment IND - ✔✔Investigational drugs are allowed to be used for treatment of a
single patient while Phase II/III studies are still underway only when the manufacturer
agrees to provide the drug and the FDA issues this patient-specific IND.
✔✔Emergency Use IND - ✔✔A special category of drugs for studies invoking the
special waiver of consent for treatment studies in an emergency setting. A set of rules
under which therapeutic trials in an emergency setting can be done. These rules
provide for a community consultation in lieu of individualized consent and restrict the
research to a very serious condition under circumstances that preclude getting
surrogate consent in a timely manner.
,✔✔Anonymous Samples - ✔✔Samples collected without direct identifiers and involve
the lowest level of risk.
✔✔Anonymized Samples - ✔✔Samples that were originally collected with direct
identifiers and from which the identifiers have been irretrievably stripped from the
sample and replaced with a random code.
✔✔Identified Samples - ✔✔Samples in which the identity of the donors can be readily
ascertained.
✔✔Coded or Linked Samples - ✔✔Samples where the direct identifier is replaced with a
code and a key to the code exists. These samples are the most used in research.
✔✔Placebo - ✔✔Any medical treatment that is inactive for the condition being
evaluated other than the effect which may result from a person's thinking that he or she
may be receiving an active treatment.
✔✔Historical Control Group - ✔✔A control group that is chosen from studies that were
completed in the past.
✔✔Noninferiority Trial - ✔✔A trial that uses active treatment control where the goal is to
show that the study drug is not less effective than the control by more than a defined
amount.
✔✔Intrapatient Dose Escalation - ✔✔A dosing scheme that allows patients to be given
successively higher doses of an experimental drug if the initial dose administered
proves to be well tolerated but unable to achieve the efficacy target.
✔✔Benefit - ✔✔The positive value or advantage of being part of the research study.
✔✔Nuremberg Code - ✔✔Ten points (not law) determined to be essential for
conducting research with humans. Summarized, they include:
*Informed consent
*Research should be based on prior animal work
*Risks should be justified by anticipated benefits
*Only qualified scientists may conduct research
*Physical/mental suffering must be avoided
*Research in which death or disabling injury is expected should not be conducted
✔✔Declaration of Helsinki - ✔✔1964 World Medical Association code of research ethics
that reinterpreted Nuremberg Code, specifically with regard to clinical trials with
therapeutic intent. Subsequently, journal editors required research be conducted in
accordance with the declaration.
, ✔✔Beecher Article - ✔✔1966 Dr. Henry K Beecher (anesthesiologist) wrote an article in
NEJM describing 22 studies with controversial ethics that had been conducted by
reputable researchers and published in major journals.
✔✔Willowbrook Hepatitis Study - ✔✔1956 Willowbrook - an institution for mentally
retarded children - initiated a study to determine the natural history of viral hepatitis, and
to test the effectiveness of gamma globulin as an agent for innoculating against
hepatitis. Children were deliberately infected with a mild form of hepatitis. Ethical
problems: exploitation of vulnerable population, withholding risk information, coercion.
✔✔Jewish Chronic Disease Study - ✔✔1963 liver cancer cells were injected into senile
patients without their knowledge as part of a study of immunity to cancer. Researchers
believed cells would be rejected, so did not think it was necessary to frighten the
patients by telling them. Ethical problems: lack of informed consent, vulnerable
population.
✔✔San Antonio Contraception Study - ✔✔1971 Mexican-American women seeking
contraceptives from a clinic participated in a study that involved taking oral birth control
then crossover to placebo. Subjects were not informed of the crossover. Ten of 76
participants became pregnant. Ethical problems: lack of informed consent, vulnerable
population, risks outweighed benefits.
✔✔Milgram Study - ✔✔1963 a series of social psychology experiments conducted by
Yale University psychologist Stanley Milgram. They measured the willingness of study
participants, men from a diverse range of occupations with varying levels of education,
to obey an authority figure who instructed them to perform acts conflicting with their
personal conscience (administering electric shocks to a subject who was allied with the
research and who pretended to feel pain) ; the experiment found, unexpectedly, that a
very high proportion of people were prepared to obey, albeit unwillingly, even if
apparently causing serious injury and distress. Ethical problems: deception,
unanticipated psychological harms
✔✔Public Health System Syphilis Study - ✔✔1932-1971 PHS study designed to
document the natural history of syphilis in African-American men. At the time the study
was initiated, there was no known treatment for syphilis. Men were recruited without
truly informed consent, and received "treatments" such as spinal taps that had no real
curative intent. After penicillin was found to be safe and effective treatment for syphilis
in the 1940s, the men in the study were denied antibiotics. The study resulted in 28
deaths, 100 cases of disability and 19 cases of congenital syphilis. Ethical problems:
lack of informed consent, deception, withholding information, withholding treatment,
putting men and their families at risk, exploitation of a vulnerable population who would
not benefit from participation.
✔✔The National Commission/The National Research Act - ✔✔1974 Congress
authorized the formation of the National Commission for the Protection of Human
